脑胶质瘤p16基因的纯合性缺失、高甲基化、突变及表达  

Homozygous Deletion, Hypermethylation, Mutation,and Expression of p16 Gene in Human Gliomas

作　　者：焦保华[1] 浦佩玉[2] 何瑞荣[3] 

机构地区：[1]河北医科大学第二医院神经外科,河北石家庄050000 [2]天津医科大学总医院神经外科,天津300052 [3]河北医科大学基础医学研究所生理学研究室,河北石家庄050017

出　　处：《癌症》2001年第7期730-733,共4页Chinese Journal of Cancer

摘　　要：目的：研究p16基因在脑胶质瘤中的纯合性缺失、高甲基化和突变等结构变化及其与表达之间的关系。方法：应用聚合酶链反应（polymerase chain reaction,PCR）和PCR甲基化银染分析技术（PCR-methylation assay with silver staining,PCR-MASS）对50例脑胶质瘤标本进行了p16基因纯合性缺失和甲基化检测；用PCR-SSCP和DNA测序技术进行了p16基因突变分析；用免疫组化检测了p16蛋白的表达。结果：50例脑胶质瘤中23例p16蛋白表达阳性，27例表达阴性，表达缺失率54％；9例（18％）纯合性缺失、7例（14％）高甲基化、2例（4％）突变。结论：p16基因在脑胶质瘤中有多种形式的结构异常，其结构的变化使p16蛋白表达障碍。p16基因纯合性缺失和高甲基化是基因失活的重要机制，在脑胶质瘤的发生、发展中起重要作用。Objective：This study was designed to investigate the homozygous deletion, hypermethylation, and mutation of p16 gene in human gliomas and the relationship between the structure and expression of p16 gene . Methods：Polymerase chain reaction (PCR) and PCR-methylation assay with silver staining(PCR-MASS) were used to detect homozygous deletion and hypermethylation of p16 gene in 50 patients with human glioma; single-stranded conformation polymorphism analysis of polymerase chain reaction products ( PCR-SSCP )and DNA sequencing were used for analysis of p16 gene mutation. Immunohistochemical analysis was used to examine the expression of p16 protein. Results：Among 50 cases of gliomas, 23 cases displayed positive protein expression of p16, 27 cases displayed negative protein expression of p16, p16 protein expression deletion rate was 54％, homozygous deletion was noted in 9 cases(18％), hypermethylation and mutation were noted in 7 cases (14％) and 2 cases (4％),respectively. Conclusion：The results demonstrate that several kinds of p16 gene structural changes exist in human gliomata. The structural changes of p16 gene cause abnormal p16 expression, the main mechanisms are hypermethylation and homozygous deletion while mutation is the secondary cause. Inactivation of p16 gene due to hypermethylation and homozygous deletion is possibly an important factor in carcinogenesis and progression of human gliomas.

关 键 词：P16基因 脑胶质瘤 基因缺失 甲基化 突变 基因表达 

分 类 号：R739.4[医药卫生—肿瘤]